1. Field of Invention
The present invention is directed to a pharmaceutical composition in the form of a spray/aerosol which can be used to deliver unpalatable compounds, such as NSAIDs. In particular, the present invention is directed to a flurbiprofen-based spray.
2. Background and Related Art
Flurbiprofen is a member of the phenylalkanoic acid derivative family of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat inflammation and pain. It is predominately used in the treatment of rheumatoid arthritis due to its anti-inflammatory effect.
Flurbiprofen is very insoluble in low pH aqueous solution, and its solubility increases slightly as the pH increases. Flurbiprofen has varying solubility in different organic solvents. Different formats and applications of flurbiprofen have been developed, such as flurbiprofen lozenges used in the treatment of sore throats. Mouthwashes containing flurbiprofen have also been developed; as well as mouth sprays that deliver a low (<0.5% w/v) level of the active
Flurbiprofen is known for producing a burning sensation in the buccal cavity (the mouth). This flurbiprofen related burn is extremely unpleasant causing an irritating prickly sensation at the back of the throat as well as a cough, gag, tickle or irritation depending on its concentration. It is desirable to reduce this ‘burn’ in flurbiprofen-containing products, and there has been considerable effort in this area. For example, there has been much effort in developing flavors that mask the burn with various flavors. The absence of taste receptors at the back of the throat and the ineffectiveness of flavors to cover the burn appear to confirm that the issue to be addressed is the irritating effect of flurbiprofen on pain receptors at the back of the throat.
Cyclodextrins are a family of compounds which are saccharide polymers. These sugar derivatives are formed from differing numbers of sugars bound together to form a cyclic oligosaccharide. As can be seen below α-CD consists of 6 membered sugar ring while β-CD and γ-CD consist of a 7 and 8 membered sugar ring respectively. Cyclodextrins are produced from starch by means of enzymatic conversion. The cyclic structure provides the cyclodextrin molecule with a large surface area, and also allows other smaller molecules to enter it forming an inclusion complex; this provides endless potential uses for cyclodextrins.
The cyclodextrin's ability to form complexes by “encapsulating” other molecules has plenty of applications, such as in drug delivery systems.
Liquid compositions which comprise an NSAID and a cyclodextrin are known in the art. For example, WO 92/00725 discloses compositions which contain ketoprofen, a cyclodextrin and dimethyl isosorbide. The presence of the isosorbide provides the composition with anti-plaque properties and enhances the anti-inflammatory properties.
WO 95/04528 discloses powder compositions containing a complex of an NSAID and a cyclodextrin for re-formulation with water to form a drink. The composition requires the presence of an acid/base couple to ensure that the complex of NSAID and cyclodextrin dissolves. A similar composition is described in WO 95/07104.
U.S. Pat. No. 5,042,997 describes an ibuprofen-containing liquid. The compositions disclosed therein are not suitable for use in a spray format. A similar composition is described in WO 2005/079858.
EP 1 574 221 describes an injectable composition which comprises diclofenac. Similarly, WO 2009/089269 describes a method of treating pain in subjects with increased risk of significant blood loss. The compositions disclosed therein comprise diclofenac and a cyclodextrin, and are most suitable for injection.
EP 1 974 751 discloses a composition which comprise an NSAID, a cyclodextrin and an amine. The presence of the amine results in the formation of an amine salt which improves the solubility of the NSAID.
Yet, none of these prior art documents describes a composition which is suitable for use as a spray to treat sore throat.
Liquid compositions which comprise an NSAID and a cyclodextrin are known in the art. Typically, these compositions can be in the form of powders that require reconstitution to form a product in the form of a consumable drink or an injectable liquid. Prior art compositions can also include specific excipients which either enhance their anti-inflammatory effect or improve the solubility of the NSAID.
Yet, none of these prior art documents describes a composition which is suitable for use as a spray to treat sore throat.